An estimated 50 million, or one in five, Americans suffer from allergies. Food allergies cause more than 200 deaths each year, and costs estimated $4,184 annually for each child, or around $25 billion overall (Gupta et al., (2013), JAMA Pediatr, 167:1026-1031). In the U.S., asthma affects 25 million people. On an annual basis, asthma directly causes more than 3,300 deaths, indirectly contributes to an additional 7,000 deaths, and costs $56 billion. Approximately 10% of sufferers have severe asthma, which has the highest morbidity and mortality, and consumes over 50% of the health care expenditure attributed to asthma. Severe asthma patients require large doses of corticosteroids in combination with other potentially toxic medications and still may suffer serious symptoms and frequent life-threatening asthma attacks. As a result, severe asthma seriously affects quality of life. According to a 2009 survey of severe asthma conducted by the Asthma and Allergy Foundation of America (AAFA), over a third of patients had made at least 5 emergency department visits and 14% had visited emergency departments twenty times or more. Half of respondents did not consider their current medications effective, two-thirds disliked the cost, and 41% disliked the side-effects. Over half of respondents would prefer to have a “drug-free option” for their asthma (Severe Asthma Survey. Asthma and Allergy Foundation of America; 2009). Allergic immune responses trigger the disease in two thirds of patients with asthma and up to 50% of patients with severe asthma (“The ENFUMOSA cross-sectional European multicenter study of the clinical phenotype of chronic severe asthma”, European Network for Understanding Mechanisms of Severe Asthma, Eur Respir J. 2003; 22(3):470-7).
Allergic reactions are initiated when allergens cross-link specific IgE antibodies bound to the high-affinity receptor FcεRI on mast cells, basophils and eosinophils, thereby triggering degranulation that results in release of inflammatory chemical mediators. IgE therefore plays a central role in allergic asthma and presents an attractive target for therapeutic intervention.
The only drug that targets IgE today is omalizumab (Xolair) for severe allergic asthma. Omalizumab is an IgE-specific humanized monoclonal antibody that depletes IgE. The drug, however, has a relatively short half-life of 1 to 4 weeks (Belliveau et al. (2005), MedGenMed 7:27) an therefore requires repeated administration at high doses (two 150 mg vials every four weeks for most adults), and costs close to $20,000 per year (Kochenderfer et al., (2010), Blood 116:4099-4102). A 2007 analysis concluded that omalizumab was not cost-effective for adults with severe asthma (Wu et al., J Allergy Clin Immunol. 2007; 120(5):1146-52).
Thus, better approaches for treatment of atopic diseases such as allergic asthma are required. In particular, an approach that persistently suppresses the IgE level over a long period of time with a single treatment would be highly desirable.